Abstract:
:Cell death is achieved by two fundamentally different mechanisms: apoptosis and necrosis. Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized. We show here that Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release. This Fas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP). RIP is also required for necrotic death induced by tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL). In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling. Thus, Fas, TRAIL and TNF receptors can initiate cell death by two alternative pathways, one relying on caspase-8 and the other dependent on the kinase RIP.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Holler N,Zaru R,Micheau O,Thome M,Attinger A,Valitutti S,Bodmer JL,Schneider P,Seed B,Tschopp Jdoi
10.1038/82732keywords:
subject
Has Abstractpub_date
2000-12-01 00:00:00pages
489-95issue
6eissn
1529-2908issn
1529-2916journal_volume
1pub_type
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